POS1106 MEDIATORS OF THE EFFECT OF THERAPEUTIC EXERCISE ON PAIN AND FUNCTION IN PATIENTS WITH KNEE AND HIP OSTEOARTHRITIS; AN INDIVIDUAL PATIENT DATA MEDIATION STUDY FROM THE OA TRIAL BANK.
Authors: J. Runhaar, M. Holden, M. Hattle, J. Quicke, R. Riley, E. Healey, D. Van der Windt, K. Dziedzic, M. Van Middelkoop, S. M. A. Bierma-Zeinstra, N. Foster
Journal: Annals of the Rheumatic Diseases (2022)

Background Currently, there is no cure for osteoarthritis (OA). Therapeutic exercise is recommended in all international guidelines to improve pain and function (1). However, randomised controlled trials (RCTs) investigating therapeutic exercise showed that, on average, effect sizes are small to moderate compared to non-exercise controls (2-3). Better knowledge about how therapeutic exercise works to improve pain and function could help improve the design and delivery of future therapeutic exercise interventions and potentially improve patient outcomes. Objectives To evaluate the mediating effects of 1) muscle strength, proprioception, and range of motion (ROM) among patients with knee OA, and 2) muscle strength among patients with hip OA, using the procedures established for Individual Participant Data (IPD) analyses by the OA Trial Bank. Methods Relevant IPD were sought from all published RCTs comparing therapeutic exercise to a non-exercise control group among people with knee and/or hip OA, using previously published methods (4). For each potential mediator separately, the effect of exercise on the absolute change in pain/function directly after the intervention was determined, controlling for the relative change in mediator under investigation and potential mediator-outcome confounders, using the ‘counterfactual framework’ (5). Next, the effect of exercise on the relative change in the mediator was determined. The percentage mediated was calculated by dividing the natural indirect effect by the total effect. Results We obtained IPD from 12 RCTs and 1407 participants (knee OA = 1113; hip OA n=294) that were eligible for inclusion in one or more mediation analyses. Therapeutic exercise showed a significant effect on the relative change in muscle strength in knee OA, but not for proprioception or ROM in knee OA, nor for muscle strength in hip OA. Of all mediators, only the change in muscle strength had a significant effect on the change in pain in knee OA, and on function in knee OA and in hip OA. The percentage mediated for each mediator and each outcome was small (5.3% or less, see Table 1). Table 1. Percentage mediated for all potential mediators, by outcome and joint. Knee OAPain Knee OAFunction Hip OAPain Hip OAFunction Muscle strength 2.4% 2.3% absent absent Proprioception absent 0.2% - - Range of motion 1.8% 5.3% - - ‘absent’: no percentage mediated calculated, since direct and indirect effect had opposite directions. ‘-‘: factors not considered a potential mediator for therapeutic exercise in hip OA. Conclusion In the first IPD mediation analysis to our knowledge of this scale, muscle strength, proprioception and ROM did mediate the effect of therapeutic exercise for pain and function in knee OA, but only to a very small degree. We observed no such mediating effect of muscle strength for therapeutic exercise in patients with hip OA. The challenge remains to better understand the key mechanisms of action of therapeutic exercise for knee and hip OA, so that exercise interventions can be designed and delivered to target these and therewith optimise the effects for patients. References [1]Bierma-Zeinstra S, et al. Nonpharmacological and nonsurgical approaches in OA. Best Pract Res Clin Rheumatol. 2020 Apr;34(2):101564. [2]Fransen M, et al. Exercise for osteoarthritis of the knee. Cochrane Database Syst Rev. 2015 Jan 9;1:CD004376. [3]Fransen M, et al. Exercise for osteoarthritis of the hip. Cochrane Database Syst Rev. 2014 Apr 22(4):CD007912. [4]Holden MA, et al. Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA): a systematic review update and individual participant data meta-analysis protocol. BMJ Open. 2017 Dec 22;7(12):e018971. [5]VanderWeele TJ, Vansteelandt S. Mediation Analysis with Multiple Mediators. Epidemiol Methods. 2014 Jan;2(1):95-115. Acknowledgements We thank all members of the OA Trial Bank Exercise Collaborative, who shared IPD with the OA Trial Bank/STEER OA for making this study possible. Disclosure of Interests Jos Runhaar Grant/research support from: Fellowship from the Foundation for Research in Rheumatology (FOREUM), Melanie Holden Grant/research support from: Grant from the Chartered Society of Physiotherapy Charitable Trust (grant no PRF/16/A07), and the National Institute for Health Research (NIHR) School of Primary Care Research (grant no 531), Miriam Hattle: None declared, Johny Quicke Grant/research support from: JQ is part-funded by an NIHR CRN West Midlands Research Scholarship and part funded by the Haywood Foundation, Richard Riley: None declared, Emma Healey Grant/research support from: part funded by the National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) West Midlands., Danielle van der Windt: None declared, Krysia Dziedzic: None declared, Marienke Van Middelkoop: None declared, S.M.A. Bierma-Zeinstra Grant/research support from: OA Trial Bank received long-term funding by the Dutch Arthritis Association, Nadine Foster: None declared